www.santpaumemoryunit.com
Alzheimer´s disease: the next
challenge in Down syndrome
Neuroimage Core
Memory Unit Sant Pau
Outline
1. Alzheimer´s disease in Down syndrome
1. A population based health plan to detect and treat
AD in DS
3. The Down Barcelona Neuroimaging Initiative
(DABNI) project
4. Some good news in Down syndrome
Alzheimer´s disease
in
Down syndrome
Life expectancy in Down syndrome
Lisa Wade. CDC data, 2010Bittles, Glasson et al. 2004
Life expectancy in Australian population Median age of people with DS by race (US)
DS is a vulnerable population that needs more care and healthservices than the general population
Alzheimer´s disease is the main medical
problem in adults with DS
IWG-2. Lancet Neurol. 2014
Down syndrome is now conceptualized as a form of genetically determined Alzheimer´s disease
McCarron et al. JIDR 2017
How is Alzheimer´s disease in
Down syndrome?
In short: “THE SAME” (with some small differences)
Fortea et al. Lancet 2020
Imaging signature of AD in DS
A population based health plan to
detect and treat AD in DS
Annual NRL & NPS
Blood (+/-) EEG
Health plan foradults with DS
in Catalonia
CLINICAL COHORT
N > 800
Alzheimer´s
Down Unit
1. To reach out for those
who cannot come to
Barcelona (or are too ill
to come to the clinic)
2. To help centers working
with DS individuals
DAVIS
"Domiciliary Alzheimer Visiting in Down syndrome”
The Down Barcelona Neuroimaging
Initiative (DABNI) project:
A research program to fight Alzheimer´s
disease in Down syndrome
Proposal
Annual NRL & NPSBlood (+/-) EEG
Health plan for adultswith DS in Catalonia
CLINICAL COHORT
BIOMARKER COHORT
CSF study Structural and functional MRI
FDG-PETFlorbetarpir-PET
Tau-PET
PolysomnographyPlasma & genetics Brain banking
N= 408 N= 157 N= 171 FDG, N= 123FBP, N= 56
N= 74 N= 13
N > 800
(Down Alzheimer Barcelona
Neuroimaging Initiative)
DABNI
Why should we care about research
in Down syndrome?
17-12-2008 17-02-2010 07-04-2011
AD dementia diagnosis is especially difficult in the context of
Down syndrome
Why biomarkers?
Biomarkers
Biomarkers for AD diagnosis in DS
Good plasma biomarkers are already here!
Fortea et al. Lancet Neurology 2018
Plasma
Carmonaet al. JAD. 2017
CSF
Longitudinal plasma NfL levels in Down syndrome
LUM (Munich J. Levin)
10 samp/5 subj
LonDownS (Strydom)
34 samp /17 subj
FJL (Paris; PI: A. Rébillat)
76 samp /31 subjects
★★
★★★
Multicenter international study: 608 samples from 236 participants
★
U. of Cambridge (PI S.Zaman)
20 samp /10 subjects
Hospital Sant Pau (J. Fortea)
275 samp/113 subjects
U. of Kentucky (L. Head)
193 samp/ 60 subjects
Objectives
1. To confirm the dx performance of plasma NfL levels
2. To assess the px performance of plasma NfL levels
3. To assess the longitudinal trajectory of plasma NfL
Prognostic performance
Clinical progression to symptomatic AD is higher in
those adults with DS with elevated plasma NfL levels
AD
Natural history
in DS
AD biomarker changes in DS
Changes with respect age
Fortea et al. Lancet 2020
Changes along the AD continuum
Trajectory of changes strikingly
similar to that in ADAD
Under review
Symptom onset
Bateman et al. Nejm 2012Fortea et al. Lancet 2020
There are very good news in
AD research in DS!
- Collaborative efforts
- Trial Ready Cohorts
- Clinical Trials
International consortia
ABC consortiumACTC-DSLumind
Horizon 21
EuropeUSA
A network of 15 international clinical sites with experience in
AD and DS clinical research. $4.7 Million award from NIH
ACTC-DS: A CLINICAL TRIALS
PLATFORM TO PREVENT AD IN DS
Trial Ready Cohort
RandomizeTreatment
Placebo
Trial Ready Cohort
Down Syndrome
(TRC-DS)
RCT 1
RandomizeTreatment
Placebo
RCT 2
RandomizeTreatment
Placebo
RCT 3
NIH DS
Connect
Registry
Direct
Recruitment
Alzheimer’s Biomarker Consortium
Down Syndrome
(ABC-DS)
European
Cohorts
Anti-amyloid (and tau) therapies must be tested in DS
APP
C99
g
Ab
AICD
DS is all about amyloid (and tau) and the first drug
targeting amyloid is being evaluated for aproval
An phase II anti-amyloid trial is about to start in DS laterDecember 2020
What about Down syndrome?
“Virtuous Circle”
Sporadic AD
AD in DS
&
ADAD
Not being able to perform research in DS is a new form of discrimination
Take home messages
1. Down Syndrome is a form of genetically determined AD
2. Trials AD are feasible due to advancements in AD
pathophysiology and biomarker research
3. International networks & trial ready cohorts have been built
4. AD might be easier to cure in DS than in sporadic AD and itis the best population in which to perform prevention studies
5. Clinical trials are about to start in DS!
www.santpaumemoryunit.comRafael Blesa
Juan Fortea
Jordi Clarimón
Daniel Alcolea
Olivia Belbin
Oriol Dols
María Carmona
Roser Ribosa
Ignacio Illán
Isabel Barroeta
Susana Fernández
Teresa Estellés
Miren Altuna
Miguel Santos
Isabel Sala
Mª Belén Sánchez
Andrea Subirana
Susana Fernández
Laura Videla
Bessy Benejam
Lídia García
Sònia Sirisi
Eduard Vilaplana
Jordi Pegueroles
Víctor Montal
Alex Bejamin
Laura Cervera
Marta Querol
Laia Muñoz
Raúl Núñez
Soraya Torres
Sílvia Valldeneu
Concepción Escolá
Constance Delaby
Alberto Lleó
@SantPauMemory